INFLUENCE OF IMMUNOTHERAPY (IL2+LAK + INHIBITION OF PROSTAGLANDIN SYNTHESIS) ON PERIPHERAL-BLOOD IMMUNE PARAMETERS AND INVITRO CYTOKINE PRODUCTION IN METASTATIC RENAL-CELL CARCINOMA

Previous results on the peripheral blood immune status of renal cell carcinoma had indicated immunosuppression in metastatic disease, possibly mediated by prostaglandin E2 (PGE2). In the present study the immunologic effects of inhibition of PG synthesis by piroxicam in combination with interleukin 2 (IL 2) + lymphokine-activated killer (LAK) cell therapy were tested by immunomonitoring. In additon to peripheral blood parameters (lymphocyte subpopulations, neopterin, beta2-microglobulin, TNF, IL 1, IFNgamma) we recorded in vitro cellular activity by incubating the patients' peripheral blood mononuclear cells (PBMC) in media containing fetal calf serum (FCS) or autologous serum, and either IL 2 or buffer. After 24 h of incubation we measured PGE2 and cytokine levels in supernatants. Systemic application of IL 2 induced in vivo lymphocyte proliferation and clearly influenced the serum levels of neopterin, beta2-Microglobulin and TNF. There was minor affection of IFNgamma and none of IL 1. PBMC in vitro produced high amounts of PGE2, IL 1 and TNF pretherapeutically, during therapy in vitro synthesis of these parameters decreased. Consistent production of IFNgamma was detected in supernatants only when FCS and IL 2 were added to the medium. Lack of affection of IFNgamma production in the autologous system during therapy indicated impaired cellular activity, which could neither be improved by therapy of the patient using IL 2 nor by adding IL 2 to the culture medium. Immunosuppression seems to interfere in a complex way with immunotherapy. Therapeutical influence of immunosuppression based on the results of immunomonitoring, however, seems to be a promising strategy for improving the still limited clinical results of immunotherapy.